Wang Yu, Kong Xiangyi, Guo Yi, Wang Renzhi, Ma Wenbin
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA.
Medicine (Baltimore). 2017 Mar;96(10):e6261. doi: 10.1097/MD.0000000000006261.
In glioblastoma multiforme (GBM), both temozolomide (TMZ) and cisplatin are very active at various toxic levels. Previous studies demonstrated that cisplatin with the standard regimen of TMZ is active in patients suffering from recurrent GBM, generating a moderate level of toxicity. Also, continuous dose-intense TMZ is a helpful therapy for patients with recurrent GBM. We have conducted a research to evaluate the security and effectiveness of cisplatin with constant dose-intense TMZ for reduplicative GBM. The time to progression (TTP) and progression-free survival (PFS) at 6 months (PFS-6) was the major end point. Toxicity, overall survival, and response are the secondary end points. GBM patients who suffered from progression or relapse after surgery, radiotherapy, and chemotherapy were qualified. Cisplatin 40, 30, and 30 mg were given on days 1, 2, and 3 before the corresponding TMZ doses, respectively. Without interruption, TMZ was given at a dose of 50 mg/m on everyday basis (dose-intense) until development or progression of unacceptable side effects. A cycle was defined as 28 days. Response Assessment in Neuro-Oncology criteria were utilized to evaluate the response. Twenty-seven patients in total (median Karnofsky performance status-80, ranging from 60 to 100; average age-56 years, ranging from 24 to 78 years) were accrued in the research. PFS-12 was 11.1% (95% confidence interval [CI], -0.7% to 22.9%), and PFS-6 was 37% (95% CI, 18.8%-55.2%). Twenty-three weeks was the median TTP (95% CI, 17-29 weeks). In the 27 evaluative patients, 6 partial responses were observed with an overall response rate of 22.2% (95% CI, 6.5%-37.9%), while no complete response was obtained. Toxicity was mostly of grades 1 to 2 amongst 116 therapy cycles. Hematological and gastroenterological toxicities were the major limiting side effect found in the research. One patient has received leukopenia World Health Organization grade 4 at cycle 5 during her treatment. Eight percent of patients had grades 3 to 4 vomiting/nausea. As a valuable therapeutic option, the innovative cisplatin with continuous dose-intense regimen of TMZ incurs an acceptable level of toxicity and shows active performance in patients with recurrent GBM.
在多形性胶质母细胞瘤(GBM)中,替莫唑胺(TMZ)和顺铂在不同毒性水平下均具有显著活性。既往研究表明,顺铂联合标准TMZ方案对复发性GBM患者有效,但会产生中度毒性。此外,持续高剂量TMZ是复发性GBM患者的一种有效治疗方法。我们开展了一项研究,以评估持续高剂量TMZ联合顺铂治疗复发性GBM的安全性和有效性。主要终点为疾病进展时间(TTP)和6个月无进展生存期(PFS-6)。毒性、总生存期和缓解情况为次要终点。符合条件的GBM患者为术后、放疗及化疗后出现进展或复发者。在相应TMZ剂量前的第1、2和3天分别给予顺铂40、30和30mg。TMZ持续每日以50mg/m剂量给药(高剂量),直至出现不可接受的副作用或疾病进展。一个周期定义为28天。采用神经肿瘤学疗效评价标准评估疗效。本研究共纳入27例患者(中位卡诺夫斯基功能状态评分80分,范围60至100分;平均年龄56岁,范围24至78岁)。PFS-12为11.1%(95%置信区间[CI],-0.7%至22.9%),PFS-6为37%(95%CI,18.8%-55.2%)。中位TTP为23周(95%CI,17-29周)。在27例可评估患者中,观察到6例部分缓解,总缓解率为22.2%(95%CI,6.5%-37.9%),未观察到完全缓解。在116个治疗周期中,毒性大多为1至2级。血液学和胃肠道毒性是本研究中发现的主要限制副作用。1例患者在第5周期出现4级世界卫生组织定义的白细胞减少。8%的患者出现3至4级呕吐/恶心。作为一种有价值的治疗选择,新型顺铂联合持续高剂量TMZ方案毒性可接受,对复发性GBM患者显示出积极疗效。